Effects of phosphate-induced hyperparathyroidism and parathyroidectomy on rat kidney calcium in vivo.

The effects of a high-phosphate diet on the calcium metabolism of kidney cells were studied in intact and parathyroidectomized (PTX) rats. The control and the PTX rats were pair-fed a normal diet with a Ca/P of 2:1 or a high-phosphate diet with a Ca/P of 1:8 for 6 wk (chronic experiments) or 1, 3, and 6 days (acute experiments). Renal cell calcium metabolism was studied by chemical and kinetic analyses in kidney slices incubated in vitro. In the control rats the high-phosphate diet significantly increased kidney and mitochondrial calcium, the cytosolic and mitochondrial exchangeable calcium pools, and all calcium fluxes. In these controls, the plasma phosphate was not significantly elevated, but the parathyroid hormone (PTH) levels tended to be high. In PTX rats fed the same high-phosphate diet, the plasma phosphate was significantly elevated, but no change in renal calcium metabolism occurred. These results suggest that nephrocalcinosis was caused by elevated PTH levels and not by the elevated plasma phosphate and that the first step in the development of nephrocalcinosis is a stimulation of cellular calcium metabolism and transport.